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Preparation method and use of compound with A beta aggregation inhibition activity

A compound and active technology, applied in the field of compound preparation, can solve problems such as toxic side effects and use restrictions, and achieve strong inhibition of Aβ aggregation activity and good dose-dependent effects

Active Publication Date: 2015-08-05
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the clinical treatment drugs for AD are mainly cholinesterase inhibitors, free radical scavengers, anti-inflammatory drugs, brain cell metabolism and blood circulation improvers, calcium antagonists, etc., but these drugs have certain toxic and side effects and use limit

Method used

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  • Preparation method and use of compound with A beta aggregation inhibition activity
  • Preparation method and use of compound with A beta aggregation inhibition activity
  • Preparation method and use of compound with A beta aggregation inhibition activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Isolation, Identification and Preservation of Streptomyces X210408

[0030] The strain X210408 was isolated from the soil samples collected from Wenchang mangrove forest in Hainan Province, China, and was identified as Streptomyces sp. by taxonomic research and molecular biology research. China Center for Type Culture Collection (Address: China.Wuhan.Wuhan University), its collection number is CCTCC NO: M 2015103, and its classification is named Streptomyces X210408Streptomyces sp.X210408. The GenBank accession number of the 16S rRNA gene sequence of Streptomyces X210408 is FJ261963, and the sequence is shown in SEQ ID NO.1.

Embodiment 2

[0031] Example 2 Streptomyces X210408 large-scale fermentation and its fermentation product sample pretreatment method

[0032] Streptomyces X210408 was inoculated in ISP2 liquid medium after plate activation, 28°C, 220r / min shaking culture for 3d, inoculated into 5L OB medium according to 5% inoculum size, 28°C, 220r / min shaking culture for 7d, obtained fermentation broth. The fermentation broth was extracted three times with an equal volume of ethyl acetate, the ethyl acetate layers were combined, and concentrated under reduced pressure to dryness to obtain a crude extract. The formula of the ISP2 liquid medium is: glucose 4g / L, yeast extract 4g / L, malt extract 10g / L, and the pH value is 7.2; the formula of the OB medium is: oat flour 20g / L , beef extract 3g / L, glucose 20g / L, FeSO 4 0.4g / L, MgCl 2 4H 2 O 0.4g / L, CaCO 3 3g / L, sea salt 3g / L, pH 7.0.

Embodiment 3

[0033] Example 3 Isolation and structure confirmation of the compound shown in formula I

[0034] (1) Compound separation

[0035] The crude extract obtained in Example 2 was dissolved in a mixed solution of dichloromethane and methanol (dichloromethane:methanol=1:1, volume ratio) and then gradient eluted in 300-400 mesh silica gel, followed by volume ratio (dichloromethane:methanol) were carried out with seven eluents consisting of 100:1, 90:1, 80:1, 60:1, 40:1, 20:1, and 10:1 of dichloromethane and methanol. For elution, the elution volume of each gradient is 1L, and the eluents with a volume ratio of 60:1 and 40:1 are combined, and then the combined fractions concentrated under reduced pressure are subjected to a hydroxypropyl sephadex LH20 column layer Analysis, the eluent is 1:1 (volume ratio) of dichloromethane and methanol, collect the components containing the target compound, concentrate and then use C18 semi-preparative liquid phase separation and purification, the ...

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Abstract

The invention discloses a preparation method and use of a compound with A beta aggregation inhibition activity and belongs to the field of microbial medicines. The compound with A beta aggregation inhibition activity is shown in the structural formula I and is prepared from streptomycete X210408 with a preservation number of CCTCC NO: M 2015103 by fermentation and separation. The compound shown in the structural formula I has A beta aggregation inhibition activity and good dosage dependence. The compound can be used for preparation of an A beta aggregation inhibitor and can be used for preparing drugs for treating Alzheimer's disease and other types of dementia. The compound provides a novel approach for treating Alzheimer's disease.

Description

technical field [0001] The invention belongs to the field of microbial medicines, and in particular relates to a preparation method and application of a compound with the activity of inhibiting Aβ aggregation. Background technique [0002] Alzheimer's disease (Alzheimer's disease, AD) is a chronic brain degenerative disease, due to brain organic damage caused by brain dysfunction, memory, understanding, self-control and other progressive degradation and persistent intellectual impairment , affecting daily activities of living, is the most common type of senile dementia. In recent years, with the aging population in our country, the incidence and prevalence of AD have gradually increased. The pathogenesis and prevention of AD have gradually become a research hotspot at home and abroad, and have also received more and more medical attention. [0003] At present, the pathogenesis of AD is not completely clear, but the hallmark pathological features in the brain of AD patients ...

Claims

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Application Information

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IPC IPC(8): C12N1/20C12P21/04A61K38/12A61P25/28C12R1/465
Inventor 洪葵叶弯弯田二丽邓子新
Owner WUHAN UNIV
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